Th17 cells and PSC (?)

[Guest guest]

If Th17 cells are involved in inflammatory bowel disease (see my

posts earlier) is there any obvious link between them and PSC?

The only link I can find so far is that human Th17 cells are

characterized by an absence of expression of CCR5 (CCR5-) in

comparison to Th1 cells (which are CCR5+):

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J Immunol. 2007 Jun 15;178(12):7525-9.

Cutting Edge: Human Th17 Cells Are Identified as Bearing CCR2+CCR5-

Phenotype.

Sato W, Aranami T, Yamamura T

Department of Immunology, National Institute of Neuroscience,

National Center of Neurology and Psychiatry, Ogawahigashi, Kodaira,

Tokyo, Japan.

Recent reports have shown that IL-17-producing CD4(+) T cells (Th17

cells) belong to a distinct helper T cell lineage and are critically

involved in the pathogenesis of autoimmune diseases and allergies.

However, the chemokine receptor profile of Th17 cells remains to be

clarified. In this study, we report that human Th17 cells are

identified as CCR2(+)CCR5(-) memory CD4(+) T cells. Analysis of PBMC

from healthy donors showed that CCR2(+) cells produce much larger

amounts of IL-17 than CCR2(-) cells, indicating the preferential

expression of CCR2 on Th17 cells. Notably, CCR2(+)CCR5(-) memory CD4

(+) T cells produced a large amount of IL-17 and little IFN-gamma,

whereas CCR2(+)CCR5(+) cells reciprocally produced an enormous amount

of IFN-gamma but little IL-17. Moreover, a higher expression of T-bet

was seen in the CCR5(+) memory T cells. These results indicate that

absence of CCR5 distinguishes human Th17 cells from Th1 cells.

PMID: 17548586.

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There have been previous reports that mutations in the CCR5 gene may

be linked to PSC, although the results seem to be contradictory:

Eri R, Jonsson JR, Pandeya N, Purdie DM, Clouston AD, N, Duffy

D, EE, Fawcett J, Florin TH, Radford- GL 2004 CCR5-

Delta32 mutation is strongly associated with primary sclerosing

cholangitis. Genes Immun. 5: 444-450.

Henckaerts L, Fevery J, Van Steenbergen W, Verslype C, Yap P, Nevens

F, Roskams T, Libbrecht L, Rutgeerts P, Vermeire S 2006 CC-type

chemokine receptor 5-[DELTA]32 mutation protects against primary

sclerosing cholangitis. Inflamm. Bowel Dis. 12: 272-277.

Moreover, Hankaerts' group has recently shown that a polymorphism in

the gene encoding the CCR5 ligand RANTES (CCL5) is also associated

with PSC:

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Gut 2007;56:891-892

The RANTES –28 g polymorphism is associated with primary sclerosing

cholangitis.

Liesbet Henckaerts1, Johan Fevery2, Werner Van Steenbergen2, Chris

Verslype2, Frederik Nevens2, Yap2, Tania Roskams3,

Rutgeerts4 and Severine Vermeire4

1 Department of Gastroenterology, University Hospital Gasthuisberg,

Leuven, Belgium

2 Department of Hepatology, University Hospital Gasthuisberg, Leuven,

Belgium

3 Department of Pathology, University Hospital Gasthuisberg, Leuven,

Belgium

4 Department of Gastroenterology, University Hospital Gasthuisberg,

Leuven, Belgium

The first 150 words of the full text of this article appear below.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic

disorder commonly associated with inflammatory bowel disease (IBD).

The pathogenesis of PSC remains unknown, but bacterial translocation

from the gut to the portal circulation, resulting in activation of an

immune cascade and subsequent bile duct injury, is believed to be one

of the triggering factors. In a previous study,1 we found a

significantly lower frequency of the 32 deletion in the CC-type

chemokine receptor 5 (CCR5) gene in patients with PSC compared with

patients with IBD and healthy controls (HC), suggesting a protective

effect of this mutation on the development of PSC. Given this

association in our population, we further investigated the role of

RANTES (Regulated on Activation Normal T Expressed and Secreted, also

known as CC-motif chemokine ligand 5 (CCL5)), one of the ligands for

the CCR5 receptor.

RANTES, localised to the cytokine cluster on chromosome 17q11.2–q12,

is a . . . [Full text of this article]

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It will be of interest to see if these genetic polymorphisms in CCR5

and RANTES somehow affect the activity of Th17 cells, or perhaps

alter the balance between Th1 and Th17 cells, and regulatory T cells

(Tregs)?

Best regards,

Dave

(father of (22); PSC 07/03; UC 08/03)